There are two forms of catechol-o-methyltransferase, a membrane-bound microsomal form and a cytoplasmic form. The membrane bound form in certain tissues differs from the soluble form in pH optimum, heat stability, kinetic properties, affinity for catecholamine substrates, and induction by cold stress, 3,4-benzy pyrene or phenylhydrazine treatment. Recently, I have discovered that in dog myocardial membranes, the membrane bound COMT activity is regulated through the beta-adrenergic receptor. The major purpose of this project is to purify the membrane catechol-o-methyl transferase, characterize it, and examine the beta-adrenergic receptor regulation of the membrane bound enzyme. It is specifically proposed to: 1) Purify microsomal COMT; 2) Physicochemically, kinetically, and immunologically characterize the enzyme; 3) Characterize the beta-receptor regulation of COMT from a mechanistic viewpoint as related to beta-receptor regulation of adenylate cyclase in the same membranes.